Researchers find DNA mutation that led to change in function of gene in humans that sparked larger neocortex

Apical progenitors (APs) and basal progenitors (BPs) in an embryonic mouse and a fetal human neocortex. Credit: Florio et al. Sci. Adv. 2016;2:e1601941
(Medical Xpress)—A team of researchers at the Max Planck Institute has found what they believe is the DNA mutation that led to a change in function of a gene in humans that sparked the growth of a larger neocortex. In their paper published in the journal Science Advances, the team describes how they engineered a gene found only in humans, Denisovans and Neanderthals to look like a precursor to reveal its neuroproliferative effect.

A year ago, another team of researchers found the human gene that most in the field believe was a major factor in allowing the human brain to grow bigger, allowing for more complex processing. In this new effort, the researchers have found what they believe was the DNA change that arose in that gene.

To pinpoint that change, the researchers engineered the unique ARHGAP11B gene to make it more similar to the ARHGAP11A gene, which researchers believe was a predecessor gene—they swapped a single nucleotide (out of 55 possibilities) for another and in so doing, found the ARHGAP11B gene lost its neuroproliferative abilities. This, the team claims, shows that it was a single mutation that allowed humans to grow bigger brains. Such a mutation, they note, was not likely due to natural selection, but was more likely a simple mistake that occurred as a brain cell was splitting. Because it conferred an advantage (the ability to grow higher than normal amounts of brain cells) the mutation was retained through subsequent generations. They also point out that such a mutation would have resulted specifically in a larger neocortex—a portion of the cortex that has been associated with hearing and sight. Prior research has also found that this region of the brain is likely the part of the brain that has most recently evolved.

The researchers also note that their research showed the mutation occurring just 1 million years after the human line split from chimpanzees—which was approximately 5 to 6 million years ago. Since that time, other research has shown the human brain has experienced several growth spurts leading to advances in intelligence and the ability to reason.

AbstractThe gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex.

Related Stories

About 99 percent of human genes are shared with chimpanzees. Only the small remainder sets us apart. However, we have one important difference: The brain of humans is three times as big as the chimpanzee brain.

Huntington's disease is caused by a mutation in the Huntington's disease gene, but it has long been a mystery why some people with the exact same mutation get the disease more severely and earlier than others. A closer look ...

Cedars-Sinai research scientists have found that immune cells in the brain play a direct role in the development of amyotrophic lateral sclerosis, or ALS, offering hope for new therapies to target the neurodegenerative disease ...

Sotos syndrome is a congenital syndrome that is characterized by varying degrees of mental retardation and a large head circumference etc. It is known that 90% of Sotos syndrome patients have mutations in the NSD1 gene. This ...

Recommended for you

For the past 17 years, most scientists around the globe have been using the nucleic acid sequence, or genome, an assembly of DNA information, from primarily a single individual as a kind of "baseline" reference and human ...

About 1 percent of patients diagnosed with autism spectrum disorder and intellectual disability have a mutation in a gene called SETD5. Scientists have now discovered what happens on a molecular level when the gene is mutated ...

Recent announcements by two biotechnology companies have stoked fears that designer babies could soon be an option for those who can afford to pick and choose which features they want for their offspring. The companies, MyOme ...

Compare any two people's DNA and you will find millions of points where their genetic codes differ. Now, scientists at La Jolla Institute for Immunology (LJI) are sharing a trove of data that will be critical for deciphering ...

Over 30 years ago, Marsha and Allen Barnett lost their sons to a puzzling childhood disease that relentlessly attacked their nervous systems and sapped their energy. After five-year-old Chuckie died suddenly in 1981, doctors ...

1 comment

Maybe with the help of crispr9 we can make the next mutation on purpose and much faster each round. The machines are coming.... Moore's Law won't stop. Adapt and change or be left behind, death is the easy way out. Evolution was great to get us here with a lot of luck involved, now it is in our hands. Humans to Mars will make it more obvious soon with space, or deep space travel much more obvious.

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.